鞘内注射Na_V 1．8反义寡核苷酸对慢性神经病理性疼痛大鼠的镇痛作用  

Effects of intrathecai Na_V 1.8 antisense oligonucleotide on chronic neuropathic pain in rats

作　　者：刘甬民[1] 姚尚龙[1] 宋文阁[2] 王月兰[1] 刘东[1] 曾涟[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院麻醉科,武汉430022 [2]山东省立医院疼痛科

出　　处：《中华麻醉学杂志》2006年第3期272-275,共4页Chinese Journal of Anesthesiology

摘　　要：目的探讨鞘内注射NaV 1．8反义寡核苷酸对慢性神经病理性疼痛大鼠的镇痛作用。方法雄性SD大鼠24只,随机分为4组(n=6):Ⅰ组(CCI+生理盐水组);Ⅱ组(CCI+Nay1．8错义寡核苷酸45μg组);Ⅲ组(CCI+NaV 1．8反义寡核苷酸45μg组);Ⅳ组(CCI+NaV 1．8反义寡核苷酸90 μg组)。按Bennett法制作CCI模型,CCI 5d鞘内置管,CCI 8 d开始鞘内给药,每日给药2次,连续5d。于CCI前2d和CCI 1、3、5、7、9、11、13 d测定机械痛阈和热痛阈,CCI 14d取双侧L4-6背根神经节 (DRG),测定钠通道NaV 1．8 mRNA的表达。结果与CCI前2 d前比较,Ⅰ、Ⅱ组在CCI 5-13 d术侧机械痛阈降低,热痛阈缩短;Ⅲ组CCI 5-13 d术侧机械痛阈降低,CCI 3-9 d热痛阈缩短,Ⅳ组CCI 5 -9 d术侧机械痛阈降低,CCI 3-7 d热痛阈缩短(P<0．05或0．01)。与Ⅰ、Ⅱ组比较,Ⅲ、Ⅳ组CCI 11、13 d术侧机械痛阈增加,热痛阈延长(P<0．05或<0．01)。CCI 14 dⅢ、Ⅳ组术侧DRG中NaV 1．8 mRNA表达低于Ⅰ、Ⅱ组(P<0．01),Ⅳ组DRG NaV 1．8 mRNA表达低于Ⅲ组(P<0．01)。结论鞘内注射45、90μg/次NaV 1．8反义寡核苷酸对大鼠神经病理性疼痛有镇痛作用,90μg/次剂量效果较好,其机制是通过下调DRG中NaV 1．8 mRNA钠通道表达实现。Objective To investigate the effects of intrathecal （IT） Nay 1.8 antisense oligonucleotide on the chronic neuropathic pain induced by chronic constrictive injury （CCI） to the sciatic nerve. Methods Twentyfour male SD rats were randomly divided into 4 groups （ n = 6 each） ： group Ⅰ CCI ＋ NS 5 μl; group Ⅱ CCI ＋ mismatch oligonucleotide 45 μg; group Ⅲ CCI ＋ antisense oligonucleotide 45 μg and group Ⅳ CCI ＋ antisense oligonucleotide 90 μg. CCI was produced by placing 4 loose ligatures on the left sciatic nerve at 1 mm interval with 4-0 chromic catgut as described by Bennett. On the 5th day after CCI IT catheter was inserted at the level of lumbar spine and identified by free flow of CSF. On the 8th day after CCI normal saline or mismatch or antisense oligonucleotide was injected IT twice a day for 5 consecutive days. Threshold to noxious thermal and mechanical stimuli was measured before CCI （baseline） and on the 1st, 3th, 5th, 7th, 9th, 11th and 13th day after CCI. On the 14th day after CCI the lumbar segment of spinal cord was removed for determination of Nay 1.8 sodium channel expression in L4-6 dorsal root ganglion （DRG） by semi-reverse transcriptase-PCR.Results The threshold to yon Frey hair stimulation and noxious thermal stimuli on the operated side was significantly lowered after CCI. On the 11th and 13th day after CCI the threshold to mechanical and thermal stimuli were significantly higher in group Ⅲ and Ⅳ than in group Ⅰ and Ⅱ . Conclusion IT Nav 1.8 antisense oligonucleotide can reduce the neuropathic pain by down-regulating Nay 1.8 mRNA expression.

关 键 词：反义寡核苷酸类 神经痛 鞘内注射 疼痛 

分 类 号：R741[医药卫生—神经病学与精神病学]